Bulbar dysfunction inevitably develops in the course of amyotrophic lateral sclerosis (ALS), and approximately 25% of patients have predominantly bulbar symptoms at the time of disease onset. In addition to characterizing the evolution in muscle architecture that could underlie associated orofacial weakness, identifying new biomarkers is critical to the development and testing of novel therapeutic agents. As painless, non-invasive, portable technologies, quantitative ultrasonography (QUS) and electrical impedance myography (EIM) could meet the need for objective measures of bulbar dysfunction. In QUS, acoustic energy is applied to a muscle of interest; the resultant raw gray-scale or backscatter pictorial data are translated into a single value that reflects the health of the image muscle. Similarly, in EIM, a high-frequency, low-intensity alternating electrical current is applie to individual muscles, and the resulting voltages measured. Impedance values reflect changes in muscle architecture, including fiber atrophy, inflammation, and the replacement of muscle with fat or connective tissue. Both of these user-friendly methods can provide sensitive indicators of neuromuscular disease status when applied to the limbs. Although they have also been used to evaluate orofacial muscles in healthy volunteers and patients with primary muscle disorders, they have not yet been systematically studied in the ALS community. We hypothesize that quantitative ultrasonography (QUS) and electrical impedance myography (EIM) measurements can provide consistent, clinically meaningful information about orofacial muscle health in ALS. In a longitudinal natural history study of 32 individuals with ALS and 32 healthy subjects, we will test this hypothesis via three aims: 1.) To assess the reliability of orofacial QS and EIM in individuals with and without ALS; 2) To determine how the measurements of selected orofacial muscles in individuals with ALS evolve over an 18-month period; 3) To evaluate preliminarily whether orofacial QUS and EIM measurements in ALS patients correlate with results of functional tests. If QUS and EIM do provide reliable, meaningful surrogate information about ALS status as expected, they could be used to make proof-of- concept therapeutic trials more efficient. Furthermore, the innovative technologies could have broader application to the diagnosis and surveillance of other central and peripheral nervous system disorders with bulbar involvement.